The present invention relates to novel crystalline forms of sertraline hydrochloride, (1S-cis)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl- 1-naphthalenaminehydrochloride, denominated Forms VI through X, an amorphous form and novel, reproducible methods for preparing them and for preparing previously reported polymorphs II, III and V.
Sertraline hydrochloride, (1S-cis)4-(3,4 dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-naphthalenamine hydrochloride, having the formula 
is approved, under the trademark Zoloft(copyright), by the U.S. Food and Drug Administration, for the treatment of depression, obsessive-compulsive disorder and panic disorder.
U.S. Pat. No. 4,536,518 describes a synthesis of sertraline hydrochloride. U.S. Pat. No. 5,248,699 describes five crystalline forms of sertraline hydrochloride, designated Form I, Form II, Form III, Form IV and Form V.
U.S. Pat. No. 4,536,518 (xe2x80x9cthe ""518 patentxe2x80x9d) describes the preparation of sertraline hydrochloride with a melting point of 243-245xc2x0 C. by treating an ethyl acetate/ether solution of the free base with gaseous hydrogen chloride. The solid state properties of the sertraline hydrochloride so produced are not otherwise disclosed.
According to U.S. Pat. No. 5,248,699 (xe2x80x9cthe ""699 patentxe2x80x9d), the sertraline hydrochloride produced by the method of the ""518 patent has a crystalline form denominated xe2x80x9cForm IIxe2x80x9d. The ""699 patent discloses four other polymorphs I, III, IV, and V, and characterizes them by single crystal x-ray analysis, powder x-ray diffraction, infra-red spectroscopy, and differential scanning calorimetry. The ""699 patent reports that Form II is produced by rapid crystallization of sertraline hydrochloride from an organic solvent, including isopropyl alcohol, hexane, generally describes methods for making sertraline hydrochloride Forms I-V. According to this patent, the preferential formation of Forms I, II or IV in an acidic solution consisting of isopropyl alcohol, hexane, and acetone, methyl isobutyl ketone, glacial acetic acid, or preferably, ethyl acetate depends on the rapidity of crystallization. Form I is described as being made by crystallizing sertraline hydrochloride in an acidic solution using an organic solvent such as those listed above. The crystallization of Form I is carried out at a temperature from about 20xc2x0 C. to about the solvent reflux temperature, preferably from about 40xc2x0 to 60xc2x0 C. The only method described in this patent for making Forms II and IV is by the rapid crystallization of sertraline hydrochloride from an organic solvent such as those listed above. Slow crystallization or granulation of sertraline hydrochloride will produce Form I. Form III is described as being formed by heating Forms I, II or IV to temperatures above about 180xc2x0 C. Granulating either of Forms II, III or IV in isopropyl alcohol, ethyl acetate, hexane or any of the solvents listed above at a temperature from about 40xc2x0 to 60xc2x0 C. causes conversion to Form I. The only method described in this patent for making Form V is by sublimation of sertraline hydrochloride Form I at reduced pressure and at a temperature from about 180-190xc2x0 C. onto a condenser. However, in our hands attempts to repeat this procedure to obtain Form V have been unsuccessful.
It has now been discovered that sertraline hydrochloride Form V can be formed by crystallization from various solvents rather than by sublimation. The existence of new crystal forms of sertraline hydrochloride, denominated Forms VI, VII, VIII, IX and X, and an amorphous of sertraline hydrochloride have been discovered. Form VI is a useful intermediate in the formation of previously reported sertraline hydrochloride Forms I, II and V.
The present invention also relates to sertraline hydrochloride ethanolate and processes for making sertraline hydrochloride ethanolate.
The present invention also relates to sertraline hydrochloride methanolate and processes for making sertraline hydrochloride methanolate.
The present invention also relates to sertraline hydrochloride solvate and processes for making sertraline hydrochloride solvate.